Safety and Immunogenicity of a Heterologous Prime-Boost Ebola Virus Vaccine Regimen in Healthy Adults in the United Kingdom and Senegal.

BACKGROUND: The 2014 West African outbreak of Ebola virus disease highlighted the urgent need to develop an effective Ebola vaccine. METHODS: We undertook 2 phase 1 studies assessing safety and immunogenicity of the viral vector modified vaccinia Ankara virus vectored Ebola Zaire vaccine (MVA-EBO-Z), manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with recombinant chimpanzee adenovirus type 3 vectored Ebola Zaire vaccine (ChAd3-EBO-Z) followed by MVA-EBO-Z. Adult volunteers in the United Kingdom (n = 38) and Senegal (n = 40) were vaccinated and an accelerated 1-week prime-boost regimen was assessed in Senegal. Safety was assessed by active and passive collection of local and systemic adverse events. RESULTS: The standard and accelerated heterologous prime-boost regimens were well-tolerated and elicited potent cellular and humoral immunogenicity in the United Kingdom and Senegal, but vaccine-induced antibody responses were significantly lower in Senegal. Cellular immune responses measured by flow cytometry were significantly greater in African vaccinees receiving ChAd3 and MVA vaccines in the same rather than the contralateral limb. CONCLUSIONS: MVA biomanufactured on an immortalized duck cell line shows potential for very large-scale manufacturing with lower cost of goods. This first trial of MVA-EBO-Z in humans encourages further testing in phase 2 studies, with the 1-week prime-boost interval regimen appearing to be particularly suitable for outbreak control. CLINICAL TRIALS REGISTRATION: NCT02451891; NCT02485912.

Correction: SARS-CoV-2 and approaches for a testing and diagnostic strategy.

Correction for 'SARS-CoV-2 and approaches for a testing and diagnostic strategy' by Delyan R. Hristov et al., J. Mater. Chem. B, 2021, 9, 8157-8173, DOI: https://doi.org/10.1039/D1TB00674F.

Building an integrated serosurveillance platform to inform public health interventions: Insights from an experts' meeting on serum biomarkers.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group's insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

Heterogeneity of the Omicron variant in Senegal.

•Omicron variant continues to progress in Senegal with the appearance of new contaminations.•IRESSEF detected the first positive case of the Omicron variant on Friday, December 3, 2021.•Since this date, the number of Omicron variant infections has increased over the weeks.•Molecular surveillance of the Omicron variant allowed us to identify a strong variation of this variant in our country.

SARS-CoV-2 and approaches for a testing and diagnostic strategy.

The COVID-19 pandemic has led to an unprecedented global health challenge, creating sudden, massive demands for diagnostic testing, treatment, therapies, and vaccines. In particular, the development of diagnostic assays for SARS-CoV-2 has been pursued as they are needed for quarantine, disease surveillance, and patient treatment. One of the major lessons the pandemic highlighted was the need for fast, cheap, scalable and reliable diagnostic methods, such as paper-based assays. Furthermore, it has previously been suggested that paper-based tests may be more suitable for settings with lower resource availability and may help alleviate some supply chain challenges which arose during the COVID-19 pandemic. Therefore, we explore how such devices may fit in a comprehensive diagnostic strategy and how some of the challenges to the technology, e.g. low sensitivity, may be addressed. We discuss the properties of the SARS-CoV-2 virus itself, the COVID-19 disease pathway, and the immune response. We then describe the different diagnostic strategies that have been pursued, focusing on molecular strategies for viral genetic material, antigen tests, and serological assays, and innovations for improving the diagnostic sensitivity and capabilities. Finally, we discuss pressing issues for the future, and what needs to be addressed for the ongoing pandemic and future outbreaks.

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells.

CMV is associated with immunosenescence and reduced vaccine responses in the elderly (>70 yr). However, the impact of CMV in young adults is less clear. In this study, healthy UK and Senegalese adults aged 18-50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenovirus type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) and boosted with modified vaccinia Ankara Ebola Zaire-vectored (MVA-EBO-Z) vaccine. CMV carriage was associated with an expansion of phenotypically senescent CD4+ and CD8+ T cells expressing CD57 and killer cell lectin-like receptor G1 (KLRG1), which was negatively associated with vaccine responses in both cohorts. Ebola-specific T cell responses induced by vaccination also contained significantly increased frequencies of terminally differentiated CD57+KLRG1+ cells in CMV seropositive (CMV+) individuals. This study suggests that CMV can also affect vaccine responses in younger adults and may have a particularly marked impact in many developing countries where CMV seroprevalence is almost universal.

Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward.

Serological testing for SARS-CoV-2 has enormous potential to contribute to COVID-19 pandemic response efforts. However, the required performance characteristics of antibody tests will critically depend on the use case (individual-level vs. population-level).

CD4 results with a bias larger than hundred cells per microliter can have a significant impact on the clinical decision during treatment initiation of HIV patients.

BACKGROUND: CD4 counts are currently used to assess HIV patients for treatment eligibility and to monitor antiretroviral response to treatment. The emerging point-of-care devices could fill an important gap in resource-limited settings. However, the accuracy of CD4-counting instruments is diverse and data on how CD4 measurement errors have an impact on clinical decisions are lacking. METHODS: Clinicians were queried on the use of CD4 results in their clinical setting. Subsequently, the effect of CD4 measurement errors on treatment initiation was put in a statistical model. Based on clinical CD4 databases from Belgium, Cambodia, and Senegal, the percentage of unchanged clinical decisions was calculated (treatment initiation should start within a 3-month delay [one visit]) for escalating CD4 measurement errors, taking into account the strict or preventive application of CD4 thresholds at 350 or 500 cells/µl used by clinicians. RESULTS: To ensure that the treatment was initiated appropriately for at least 95% of patients, an error of 5 - 10 cells/µl was allowed. This is significantly smaller than the bias of ±50 cells/µl most clinicians considered acceptable. For limits of agreement (LOA, 1.96 x error) of 100 cells/µl, corresponding to most CD4 instrument evaluations, the misclassification rate of patients was found to be 3 - 28% at the threshold of 350 cells/µl (strict or flexible), and 13 - 20% at 500 cells/µl. CONCLUSIONS: The maximum allowed CD4 bias on results from new CD4 technologies should not exceed 50 cells/µl (LOA 100 cells/µl) when applied for treatment initiation, to ensure at least 72% of correct clinical decisions. © 2016 International Clinical Cytometry Society.

Laboratory and field evaluation of the Partec CyFlow miniPOC for absolute and relative CD4 T-cell enumeration.

BACKGROUND: A new CD4 point-of-care instrument, the CyFlow miniPOC, which provides absolute and percentage CD4 T-cells, used for screening and monitoring of HIV-infected patients in resource-limited settings, was introduced recently. We assessed the performance of this novel instrument in a reference laboratory and in a field setting in Senegal. METHODOLOGY: A total of 321 blood samples were obtained from 297 adults and 24 children, all HIV-patients attending university hospitals in Dakar, or health centers in Ziguinchor. Samples were analyzed in parallel on CyFlow miniPOC, FACSCount CD4 and FACSCalibur to assess CyFlow miniPOC precision and accuracy. RESULTS: At the reference lab, CyFlow miniPOC, compared to FACSCalibur, showed an absolute mean bias of -12.6 cells/mm3 and a corresponding relative mean bias of -2.3% for absolute CD4 counts. For CD4 percentages, the absolute mean bias was -0.1%. Compared to FACSCount CD4, the absolute and relative mean biases were -31.2 cells/mm3 and -4.7%, respectively, for CD4 counts, whereas the absolute mean bias for CD4 percentages was 1.3%. The CyFlow miniPOC was able to classify HIV-patients eligible for ART with a sensitivity of ≥ 95% at the different ART-initiation thresholds (200, 350 and 500 CD4 cells/mm3). In the field lab, the room temperature ranged from 30 to 35°C during the working hours. At those temperatures, the CyFlow miniPOC, compared to FACSCount CD4, had an absolute and relative mean bias of 7.6 cells/mm3 and 2.8%, respectively, for absolute CD4 counts, and an absolute mean bias of 0.4% for CD4 percentages. The CyFlow miniPOC showed sensitivity equal or greater than 94%. CONCLUSION: The CyFlow miniPOC showed high agreement with FACSCalibur and FACSCount CD4. The CyFlow miniPOC provides both reliable absolute CD4 counts and CD4 percentages even under the field conditions, and is suitable for monitoring HIV-infected patients in resource-limited settings.

WHO multicenter evaluation of FACSCount CD4 and Pima CD4 T-cell count systems: instrument performance and misclassification of HIV-infected patients.

BACKGROUND: CD4⁺ T-cell counts are used to screen and follow-up HIV-infected patients during treatment. As part of the World Health Organization prequalification program of diagnostics, we conducted an independent multicenter evaluation of the FACSCount CD4 and the Pima CD4, using the FACSCalibur as reference method. METHODS: A total of 440 paired capillary and venous blood samples were collected from HIV-infected patients attending the HIV outpatient clinic in Antwerp, Belgium, and the HIV care and treatment center in Dar es Salam, Tanzania. Capillary blood was run on Pima analyzer, whereas venous blood was analyzed on FACSCount, Pima, and FACSCalibur instruments. Precision and agreement between methods were assessed. RESULTS: The FACSCount CD4 results were in agreement with the FACSCalibur results with relative bias of 0.4% and 3.1% on absolute CD4 counts and an absolute bias of -0.6% and -1.1% on CD4% in Antwerp and Dar es Salam, respectively. The Pima CD4 results were in agreement with the FACSCalibur results with relative bias of -4.1% and -9.4% using venous blood and of -9.5% and -0.9% using capillary blood in Antwerp and Dar es Salam, respectively. At the threshold of 350 cells per microliter, the FACSCount CD4 and Pima CD4 using venous and capillary blood misclassified 7%, 9%, and 13% of patients, respectively. CONCLUSIONS: The FACSCount CD4 provides reliable CD4 counts and CD4% and is suitable for monitoring adult and pediatric HIV patients in moderate-volume settings. The Pima CD4 is more suitable for screening eligible adult HIV patients for antiretroviral treatment initiation in low-volume laboratories.